Potential Missed Opportunities for Antenatal Corticosteroid Exposure and Outcomes Among Periviable Births: Observational Cohort Study

Abstract

ABSTRACT Antenatal corticosteroid (ANCS) exposure reduces preterm infant death and morbidities, such as intracranial hemorrhage. Although observational studies suggest periviable infants may benefit from this treatment, many eligible women do not receive ANCSs due to unclear policies, lack of opportunity, or inconsistent care. Professional societies and the Eunice Kennedy Shriver National Institute of Child Health and Human Development recommend administering ANCSs at 24 weeks' gestation for all at-risk pregnancies and as early as 22 weeks with planned postnatal treatment. The aim of this study was to assess whether potential missed opportunities for ANCSs increase as gestational age decreases and are associated with higher rates of hospital mortality or severe brain injury. This was an observational cohort study of infants born at 24 National Institute of Child Health and Human Development Neonatal Research Network centers from 2006 to 2018. Included were infants at 220/7 to 256/7 weeks of gestation, without major birth defects, and a birth weight of 401 to 1000 g. Data were collected prospectively from birth to discharge, transfer, death, or 120 days. Antenatal corticosteroid exposure was defined as infants who received partial, complete, or repeat courses of the treatment. Potential missed opportunities for exposure were defined as infants who received no ANCSs, despite potentially having sufficient time to receive prenatal antibiotics, were administered magnesium sulfate, or experience prolonged rupture of membranes. Severe brain injury was defined as intracranial hemorrhage or periventricular leukomalacia on cranial imaging. The primary outcome was the rate of ANCS exposure and potential missed opportunities at each gestational age. Secondary outcomes included death and severe brain injury. A total of 7957 infants who were actively treated postnatally were included in the primary analysis. Of these, 87.6% had ANCS exposure, 5.7% had no exposure but potential missed opportunities for exposure, and 6.7% had no exposure and no potential missed opportunities. Potential missed opportunities for exposure were more common in infants born at 22 and 23 weeks versus 25 weeks (22 weeks: adjusted risk ratio [aRR], 11.06; 95% confidence interval [CI], 7.52–16.27; P < 0.001); 23 weeks: aRR, 3.24; 95% CI, 2.44–4.29; P < 0.001). No difference was observed between 24 and 25 weeks (24 weeks: aRR, 1.08; 95% CI, 0.82–1.42). From 2006 to 2018, infants at 22 weeks saw the largest increase in exposure to ANCSs (12.5%–87.2%) and a decrease in the rate of potential missed opportunities (68.8%–2.6%). Overall, the rate of mortality was 23% lower among infants in the exposure group than for those in the missed opportunities group (31% vs 54.8%; aRR, 0.77; 95% CI, 0.70–0.84; P < 0.001). Infants in the exposure group had lower risk of severe brain injury than those in the missed opportunities group (25% vs 44.5%; aRR, 0.64; 95% CI, 0.55–0.73; P < 0.001), with no significant variation by gestational age. In conclusion, the potential for missed opportunities for ANCS exposure was more common among periviable infants at 22 and 23 weeks compared with those at 25 weeks of gestation. Moreover, exposure to ANCSs was associated with lower rates of mortality and severe brain injury.